Prenatal alcohol exposure is the leading preventable cause of birth defects in the United States, producing an array of neurological, behavioral and physical abnormalities collectively known as Fetal Alcohol Spectrum Disorders (FASD). Early diagnosis of FASD is the key to effective interventions and treatments, particularly for children under the age of 3 who may benefit from early neuroplasticity and reduce the long-term adverse effects. The long-term goal of our research program is to provide the science to support routine newborn screening for prenatal alcohol exposure. The primary aim of this international U01 grant proposal is to examine the association between maternal alcohol use and newborn phosphatidylethanol (PEth) levels in their newborn children, in a country (Uruguay) where significant alcohol use is common during pregnancy. Our previous work in public health care hospitals in Montevideo, Uruguay documented high rates of alcohol use during pregnancy (60%) and PEth levels in newborns (79%). PEth is a new biomarker that detects episodic heavy drinking (3 or more drinks) in the last 30 days. The test is 100% specific in detecting recent alcohol use with no known false positives. This proposed design is a cross-sectional study that will include1500 women 18 years and older and their newborns. Women who are admitted to one of two selected public health care hospitals in Montevideo, Uruguay for obstetrical care will be recruited to participate in the study. Maternal alcohol use will be assessed using a validated measure developed by Drs. Phil May and Wilsnack. The interview schedule has become the standard measure to assess maternal alcohol use and fetal alcohol exposure in the US and other countries. Maternal alcohol biomarker assays will include ethylglucuronide (EtG) in hair and nails and PEth in blood obtained at the time of delivery. Newborn umbilical cord and routine 48 hour heel stick blood will be collected to assess newborn PEth levels. By collecting newborn PEth levels at birth and 48 hours later we can assess the PEth kinetics to determine the optimum time to measure newborn PEth levels. By comparing newborn Peth levels with maternal self-reported alcohol use and alcohol biomarkers this innovative study will provide new information on the sensitivity and specificity of PEth as a newborn biomarker of prenatal alcohol exposure. The findings from this study could have enormous public health and policy implications, should PEth prove to be a highly sensitive and specific indicator of risky prenatal alcohol exposure. Analysis of PEth in dried blood spot cards would be the first assay to identify prenatal alcohol exposure in a universally available sample of newborn blood. Future work may also help us correlate newborn PEth levels with long-term behavioral, learning and developmental deficits in children and assist in early diagnosis of children with FASD.